scholarly journals Regulation of DNA methylation on key parasitism genes of Cysticercus cellulosae revealed by integrative epigenomic-transcriptomic analyses

2018 ◽  
Author(s):  
Shumin Sun ◽  
Xiaolei Liu ◽  
Guanyu Ji ◽  
Xuelin Wang ◽  
Junwen Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Epigenetic Modification ◽  
Developmental Regulation ◽  
Taenia Solium ◽  
Host Interactions ◽  
Genome Wide ◽  
Cysticercus Cellulosae ◽  
Genes Encoding ◽  
Genome Bisulfite Sequencing ◽  
Parasitism Genes

AbstractBackgroundThe life cycle of Taenia solium is characterized by different stages of development, requiring various kinds of hosts that can appropriately harbor the eggs (proglottids), the oncospheres, the larvae and the adults. Similar to other metazoan pathogens, T. solium undergoes transcriptional and developmental regulation via epigenetics during its complex lifecycle and host interactions.ResultIn the present study, we integrated whole-genome bisulfite sequencing and RNA-seq technologies to characterize the genome-wide DNA methylation and its effect on transcription of Cysticercus cellulosae of T. solium. We confirm that the T. solium genome in the cysticercus stage is epigenetically modified by DNA methylation in a pattern similar to that of other invertebrate genomes, i.e., sparsely or moderately methylated. We also observed an enrichment of non-CpG methylation in defined genetic elements of the T. solium genome. Furthermore, an integrative analysis of both the transcriptome and the DNA methylome indicated a strong correlation between these two datasets, suggesting that gene expression might be tightly regulated by DNA methylation. Importantly, our data suggested that DNA methylation might play an important role in repressing key parasitism-related genes, including genes encoding excretion-secretion proteins, thereby raising the possibility of targeting DNA methylation processes as a useful strategy in therapeutics of cysticercosis.ConclusionOur study will provide a foundation for future studies to explore this key epigenetic modification in development of Cysticercus cellulosae and in human cysticercus disease.

scholarly journals Regulation of DNA methylation on key parasitism genes of Cysticercus cellulosae revealed by integrative epigenomic-transcriptomic analyses

Hereditas ◽  
2021 ◽  
Vol 158 (1) ◽  
Author(s):  
Xinrui Wang ◽  
Weiyi Song ◽  
Guanyu Ji ◽  
Yining Song ◽  
Xiaolei Liu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Developmental Regulation ◽  
Taenia Solium ◽  
Rna Seq ◽  
Host Interactions ◽  
Genome Wide ◽  
Cysticercus Cellulosae ◽  
Genes Encoding ◽  
Genome Bisulfite Sequencing ◽  
Parasitism Genes

Abstract Background The life cycle of Taenia solium is characterized by different stages of development, requiring various kinds of hosts that can appropriately harbor the eggs (proglottids), the oncospheres, the larvae and the adults. Similar to other metazoan pathogens, T. solium undergoes transcriptional and developmental regulation via epigenetics during its complex lifecycle and host interactions. Result In the present study, we integrated whole-genome bisulfite sequencing and RNA-seq technologies to characterize the genome-wide DNA methylation and its effect on transcription of Cysticercus cellulosae of T. solium. We confirm that the T. solium genome in the cysticercus stage is epigenetically modified by DNA methylation in a pattern similar to that of other invertebrate genomes, i.e., sparsely or moderately methylated. We also observed an enrichment of non-CpG methylation in defined genetic elements of the T. solium genome. Furthermore, an integrative analysis of both the transcriptome and the DNA methylome indicated a strong correlation between these two datasets, suggesting that gene expression might be tightly regulated by DNA methylation. Importantly, our data suggested that DNA methylation might play an important role in repressing key parasitism-related genes, including genes encoding excretion-secretion proteins, thereby raising the possibility of targeting DNA methylation processes as a useful strategy in therapeutics of cysticercosis.

scholarly journals Regulation of DNA Methylation on Key Parasitism Genes of Cysticercus Cellulosae Revealed by Integrative Epigenomic-Transcriptomic Analyses

2020 ◽  
Author(s):  
Xinrui Wang ◽  
Weiyi Song ◽  
Yining Song ◽  
Guanyu Ji ◽  
Xuenong Luo ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Developmental Regulation ◽  
Taenia Solium ◽  
Rna Seq ◽  
Host Interactions ◽  
Genome Wide ◽  
Cysticercus Cellulosae ◽  
Genes Encoding ◽  
Genome Bisulfite Sequencing ◽  
Parasitism Genes

Abstract Background: The life cycle of Taenia solium is characterized by different stages of development, requiring various kinds of hosts that can appropriately harbor the eggs (proglottids), the oncospheres, the larvae and the adults. Similar to other metazoan pathogens, T. solium undergoes transcriptional and developmental regulation via epigenetics during its complex lifecycle and host interactions.Result: In the present study, we integrated whole-genome bisulfite sequencing and RNA-seq technologies to characterize the genome-wide DNA methylation and its effect on transcription of Cysticercus cellulosae of T. solium. We confirm that the T. solium genome in the cysticercus stage is epigenetically modified by DNA methylation in a pattern similar to that of other invertebrate genomes, i.e., sparsely or moderately methylated. We also observed an enrichment of non-CpG methylation in defined genetic elements of the T. solium genome. Furthermore, an integrative analysis of both the transcriptome and the DNA methylome indicated a strong correlation between these two datasets, suggesting that gene expression might be tightly regulated by DNA methylation. Importantly, our data suggested that DNA methylation might play an important role in repressing key parasitism-related genes, including genes encoding excretion-secretion proteins, thereby raising the possibility of targeting DNA methylation processes as a useful strategy in therapeutics of cysticercosis.

scholarly journals Genome-wide identification of genes regulating DNA methylation using genetic anchors for causal inference

2019 ◽  
Author(s):  
Paul J. Hop ◽  
René Luijk ◽  
Lucia Daxinger ◽  
Maarten van Iterson ◽  
Koen F. Dekkers ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Large Scale ◽  
Population Genomics ◽  
Epigenetic Modification ◽  
Binding Activity ◽  
Dna Binding Activity ◽  
Genome Wide ◽  
Scale Population ◽  
Genes Encoding ◽  
Methylation Patterns

SUMMARYDNA methylation is a key epigenetic modification in human development and disease, yet there is limited understanding of its highly coordinated regulation. Here, we identified 818 genes that influence DNA methylation patterns in blood using large-scale population genomics data. By employing genetic instruments as causal anchors, we identified directed associations between gene expression and distant DNA methylation levels, whilst ensuring specificity of the associations by correcting for linkage disequilibrium and pleiotropy among neighboring genes. We found that DNA methylation patterns are commonly shaped by transcription factors that consistently increase or decrease DNA methylation levels. However, we also observed genes encoding proteins without DNA binding activity with widespread effects on DNA methylation (e.g. NFKBIE, CDCA7(L) and NLRC5) and we suggest plausible mechanisms underlying these findings. Many of the reported genes were unknown to influence DNA methylation, resulting in a comprehensive resource providing insights in the principles underlying epigenetic regulation.

scholarly journals Low-pass whole genome bisulfite sequencing of neonatal dried blood spots identifies a role for RUNX1 in Down syndrome DNA methylation profiles

2020 ◽  
Author(s):  
Benjamin I Laufer ◽  
Hyeyeon Hwang ◽  
Julia M Jianu ◽  
Charles E Mordaunt ◽  
Ian F Korf ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Down Syndrome ◽  
Early Life ◽  
Trisomy 21 ◽  
Bisulfite Sequencing ◽  
Dried Blood Spots ◽  
Whole Genome ◽  
Genome Wide ◽  
Low Pass ◽  
Genome Bisulfite Sequencing

Abstract Neonatal dried blood spots (NDBS) are a widely banked sample source that enables retrospective investigation into early life molecular events. Here, we performed low-pass whole genome bisulfite sequencing (WGBS) of 86 NDBS DNA to examine early life Down syndrome (DS) DNA methylation profiles. DS represents an example of genetics shaping epigenetics, as multiple array-based studies have demonstrated that trisomy 21 is characterized by genome-wide alterations to DNA methylation. By assaying over 24 million CpG sites, thousands of genome-wide significant (q < 0.05) differentially methylated regions (DMRs) that distinguished DS from typical development and idiopathic developmental delay were identified. Machine learning feature selection refined these DMRs to 22 loci. The DS DMRs mapped to genes involved in neurodevelopment, metabolism, and transcriptional regulation. Based on comparisons with previous DS methylation studies and reference epigenomes, the hypermethylated DS DMRs were significantly (q < 0.05) enriched across tissues while the hypomethylated DS DMRs were significantly (q < 0.05) enriched for blood-specific chromatin states. A ~28 kb block of hypermethylation was observed on chromosome 21 in the RUNX1 locus, which encodes a hematopoietic transcription factor whose binding motif was the most significantly enriched (q < 0.05) overall and specifically within the hypomethylated DMRs. Finally, we also identified DMRs that distinguished DS NDBS based on the presence or absence of congenital heart disease (CHD). Together, these results not only demonstrate the utility of low-pass WGBS on NDBS samples for epigenome-wide association studies, but also provide new insights into the early life mechanisms of epigenomic dysregulation resulting from trisomy 21.

scholarly journals High-resolution epigenome analysis in nasal samples derived from children with respiratory viral infections reveals striking changes upon SARS-CoV-2 infection

2021 ◽  
Author(s):  
Konner Winkley ◽  
Boryana Koseva ◽  
Dithi Banerjee ◽  
Warren Cheung ◽  
Rangaraj Selvarangan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Viral Infections ◽  
Immune Cell ◽  
Regulatory Elements ◽  
Influenza B ◽  
Monocyte Count ◽  
Genome Wide ◽  
Genome Bisulfite Sequencing ◽  
Respiratory Viral Infections ◽  
Activation Pathways

AbstractBackgroundDNA methylation patterns of the human genome can be modified by environmental stimuli and provide dense information on gene regulatory circuitries. We studied genome-wide DNA methylation in nasal samples from infants (<6 months) applying whole-genome bisulfite sequencing (WGBS) to characterize epigenome response to 10 different respiratory viral infections including SARS-CoV-2.ResultsWe identified virus-specific differentially methylated regions (vDMR) with human metapneumovirus (hMPV) and SARS-CoV-2 followed by Influenza B (Flu B) causing the weakest vs. strongest epigenome response with 496 vs. 78541 and 14361 vDMR, respectively. We found a strong replication rate of FluB (52%) and SARS-CoV-2 (42%) vDMR in independent samples indicating robust epigenome perturbation upon infection. Among the FluB and SARS-CoV-2 vDMRs, around 70% were hypomethylated and significantly enriched among epithelial cell-specific regulatory elements whereas the hypermethylated vDMRs for these viruses mapped more frequently to immune cell regulatory elements, especially those of the myeloid lineage. The hypermethylated vDMRs were also enriched among genes and genetic loci in monocyte activation pathways and monocyte count. Finally, we perform single-cell RNA-sequencing characterization of nasal mucosa in response to these two viruses to functionally analyze the epigenome perturbations. Which supports the trends we identified in methylation data and highlights and important role for monocytes.ConclusionsAll together, we find evidence indicating genetic predisposition to innate immune response upon a respiratory viral infection. Our genome-wide monitoring of infant viral response provides first catalogue of associated host regulatory elements. Assessing epigenetic variation in individual patients may reveal evidence for viral triggers of childhood disease.

scholarly journals Genome-Wide DNA Methylation Profiling in the Lotus (Nelumbo nucifera) Flower Showing its Contribution to the Stamen Petaloid

Plants ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 135 ◽  
Author(s):  
Zhongyuan Lin ◽  
Meihui Liu ◽  
Rebecca Njeri Damaris ◽  
Tonny Maraga Nyong’a ◽  
Dingding Cao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Bisulfite Sequencing ◽  
Epigenetic Modification ◽  
Nelumbo Nucifera ◽  
Flower Formation ◽  
Relationship Analysis ◽  
Genome Wide ◽  
Dna Methylation Profiling ◽  
Methylation Profiling

DNA methylation is a vital epigenetic modification. Methylation has a significant effect on the gene expression influencing the regulation of different physiological processes. Current studies on DNA methylation have been conducted on model plants. Lotus (Nelumbo nucifera) is a basic eudicot exhibiting variations during development, especially in flower formation. DNA methylation profiling was conducted on different flower tissues of lotuses through whole genome bisulfite sequencing (WGBS) to investigate the effects of DNA methylation on its stamen petaloid. A map of methylated cytosines at the single base pair resolution for the lotus was constructed. When the stamen was compared with the stamen petaloid, the DNA methylation exhibited a global decrease. Genome-wide relationship analysis between DNA methylation and gene expression identified 31 different methylation region (DMR)-associated genes, which might play crucial roles in floral organ formation, especially in the stamen petaloid. One out of 31 DMR-associated genes, NNU_05638 was homolog with Plant U-box 33 (PUB33). The DNA methylation status of NNU_05638 promoter was distinct in three floral organs, which was confirmed by traditional bisulfite sequencing. These results provide further insights about the regulation of stamen petaloids at the epigenetic level in lotus.

scholarly journals Efficient and accurate determination of genome-wide DNA methylation patterns in Arabidopsis thaliana with enzymatic methyl sequencing

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Suhua Feng ◽  
Zhenhui Zhong ◽  
Ming Wang ◽  
Steven E. Jacobsen
Keyword(s):  
Dna Methylation ◽  
Bisulfite Sequencing ◽  
Accurate Determination ◽  
Gc Content ◽  
Epigenetic Mark ◽  
Whole Genome ◽  
Whole Genome Bisulfite Sequencing ◽  
Genome Wide ◽  
A Genome ◽  
Genome Bisulfite Sequencing

Abstract Background 5′ methylation of cytosines in DNA molecules is an important epigenetic mark in eukaryotes. Bisulfite sequencing is the gold standard of DNA methylation detection, and whole-genome bisulfite sequencing (WGBS) has been widely used to detect methylation at single-nucleotide resolution on a genome-wide scale. However, sodium bisulfite is known to severely degrade DNA, which, in combination with biases introduced during PCR amplification, leads to unbalanced base representation in the final sequencing libraries. Enzymatic conversion of unmethylated cytosines to uracils can achieve the same end product for sequencing as does bisulfite treatment and does not affect the integrity of the DNA; enzymatic methylation sequencing may, thus, provide advantages over bisulfite sequencing. Results Using an enzymatic methyl-seq (EM-seq) technique to selectively deaminate unmethylated cytosines to uracils, we generated and sequenced libraries based on different amounts of Arabidopsis input DNA and different numbers of PCR cycles, and compared these data to results from traditional whole-genome bisulfite sequencing. We found that EM-seq libraries were more consistent between replicates and had higher mapping and lower duplication rates, lower background noise, higher average coverage, and higher coverage of total cytosines. Differential methylation region (DMR) analysis showed that WGBS tended to over-estimate methylation levels especially in CHG and CHH contexts, whereas EM-seq detected higher CG methylation levels in certain highly methylated areas. These phenomena can be mostly explained by a correlation of WGBS methylation estimation with GC content and methylated cytosine density. We used EM-seq to compare methylation between leaves and flowers, and found that CHG methylation level is greatly elevated in flowers, especially in pericentromeric regions. Conclusion We suggest that EM-seq is a more accurate and reliable approach than WGBS to detect methylation. Compared to WGBS, the results of EM-seq are less affected by differences in library preparation conditions or by the skewed base composition in the converted DNA. It may therefore be more desirable to use EM-seq in methylation studies.

scholarly journals Genome-Wide Differential DNA Methylation and miRNA Expression Profiling Reveals Epigenetic Regulatory Mechanisms Underlying Nitrogen-Limitation-Triggered Adaptation and Use Efficiency Enhancement in Allotetraploid Rapeseed

2020 ◽  
Vol 21 (22) ◽  
pp. 8453
Author(s):  
Ying-peng Hua ◽  
Ting Zhou ◽  
Jin-yong Huang ◽  
Cai-peng Yue ◽  
Hai-xing Song ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Epigenetic Modification ◽  
Lateral Roots ◽  
Regulatory Mechanisms ◽  
Crop Species ◽  
N Limitation ◽  
Genome Wide ◽  
Differentially Methylated Genes ◽  
N Metabolism ◽  
Use Efficiency

Improving crop nitrogen (N) limitation adaptation (NLA) is a core approach to enhance N use efficiency (NUE) and reduce N fertilizer application. Rapeseed has a high demand for N nutrients for optimal plant growth and seed production, but it exhibits low NUE. Epigenetic modification, such as DNA methylation and modification from small RNAs, is key to plant adaptive responses to various stresses. However, epigenetic regulatory mechanisms underlying NLA and NUE remain elusive in allotetraploid B. napus. In this study, we identified overaccumulated carbohydrate, and improved primary and lateral roots in rapeseed plants under N limitation, which resulted in decreased plant nitrate concentrations, enhanced root-to-shoot N translocation, and increased NUE. Transcriptomics and RT-qPCR assays revealed that N limitation induced the expression of NRT1.1, NRT1.5, NRT1.7, NRT2.1/NAR2.1, and Gln1;1, and repressed the transcriptional levels of CLCa, NRT1.8, and NIA1. High-resolution whole genome bisulfite sequencing characterized 5094 differentially methylated genes involving ubiquitin-mediated proteolysis, N recycling, and phytohormone metabolism under N limitation. Hypermethylation/hypomethylation in promoter regions or gene bodies of some key N-metabolism genes might be involved in their transcriptional regulation by N limitation. Genome-wide miRNA sequencing identified 224 N limitation-responsive differentially expressed miRNAs regulating leaf development, amino acid metabolism, and plant hormone signal transduction. Furthermore, degradome sequencing and RT-qPCR assays revealed the miR827-NLA pathway regulating limited N-induced leaf senescence as well as the miR171-SCL6 and miR160-ARF17 pathways regulating root growth under N deficiency. Our study provides a comprehensive insight into the epigenetic regulatory mechanisms underlying rapeseed NLA, and it will be helpful for genetic engineering of NUE in crop species through epigenetic modification of some N metabolism-associated genes.

scholarly journals Genome-wide DNA methylation profiles of porcine ovaries in estrus and proestrus

2018 ◽  
Vol 50 (9) ◽  
pp. 714-723 ◽  
Author(s):  
Xiaolong Zhou ◽  
Songbai Yang ◽  
Feifei Yan ◽  
Ke He ◽  
Ayong Zhao
Keyword(s):  
Dna Methylation ◽  
Epigenetic Modification ◽  
Cpg Islands ◽  
Biological Processes ◽  
Hormone Regulation ◽  
Methylated Dna ◽  
Coding Regions ◽  
Genome Wide ◽  
Differentially Methylated Genes ◽  
Flanking Regions

DNA methylation is an important epigenetic modification involved in the estrous cycle and the regulation of reproduction. Here, we investigated the genome-wide profiles of DNA methylation in porcine ovaries in proestrus and estrus using methylated DNA immunoprecipitation sequencing. The results showed that DNA methylation was enriched in intergenic and intron regions. The methylation levels of coding regions were higher than those of the 5′- and 3′-flanking regions of genes. There were 4,813 differentially methylated regions (DMRs) of CpG islands in the estrus vs. proestrus ovarian genomes. Additionally, 3,651 differentially methylated genes (DMGs) were identified in pigs in estrus and proestrus. The DMGs were significantly enriched in biological processes and pathways related to reproduction and hormone regulation. We identified 90 DMGs associated with regulating reproduction in pigs. Our findings can serve as resources for DNA methylome research focused on porcine ovaries and further our understanding of epigenetically regulated reproduction in mammals.

scholarly journals Identification and characterization of the cytosine-5 DNA methyltransferase gene family in Salvia miltiorrhiza

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4461 ◽  
Author(s):  
Jiang Li ◽  
Caili Li ◽  
Shanfa Lu
Keyword(s):  
Dna Methylation ◽  
Salicylic Acid ◽  
Gene Family ◽  
Sequence Alignment ◽  
Dna Methyltransferase ◽  
Epigenetic Modification ◽  
Salvia Miltiorrhiza ◽  
Dna Methyltransferases ◽  
Genome Wide ◽  
Wide Range

Cytosine DNA methylation is highly conserved epigenetic modification involved in a wide range of biological processes in eukaryotes. It was established and maintained by cytosine-5 DNA methyltransferases (C5-MTases) in plants. Through genome-wide identification, eight putative SmC5-MTase genes were identified from the genome of Salvia miltiorrhiza, a well-known traditional Chinese medicine material and an emerging model medicinal plant. Based on conserved domains and phylogenetic analysis, eight SmC5-MTase genes were divided into four subfamilies, including MET, CMT, DRM and DNMT2. Genome-wide comparative analysis of the C5-MTase gene family in S. miltiorrhiza and Arabidopsis thaliana, including gene structure, sequence features, sequence alignment and conserved motifs, was carried out. The results showed conservation and divergence of the members of each subfamily in plants. The length of SmC5-MTase open reading frames ranges widely from 1,152 (SmDNMT2) to 5,034 bp (SmMET1). The intron number of SmC5-MTases varies between 7 (SmDRM1) and 20 (SmCMT1 and SmCMT2b). These features were similar to their counterparts from Arabidopsis. Sequence alignment and conserved motif analysis showed the existence of highly conserved and subfamily-specific motifs in the C5-MTases analyzed. Differential transcript abundance was detected for SmC5-MTases, implying genome-wide variance of DNA methylation in different organs and tissues. Transcriptome-wide analysis showed that the transcript levels of all SmC5-MTase genes was slightly changed under yeast extract and methyl jasmonate treatments. Six SmC5-MTases, including SmMET1, SmCMT1, SmCMT2a, SmCMT2b, SmCMT3 and SmDRM1, were salicylic acid-responsive, suggesting the involvement of SmC5-MTases in salicylic acid-dependent immunity. These results provide useful information for demonstrating the role of DNA methylation in bioactive compound biosynthesis and Dao-di herb formation in medicinal plants.

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